Studies which were undertaken by the principal investigator demonstrated that: 1. Enamel Proteins seem to be a component of "root analogue" surfaces on specialized teeth (the lingual surfaces of the rabbit incisor). Preliminary evidence indicates that these proteins are also present on forming root surfaces of mouse molars, and 2. That enamel proteins are capable of eliciting autoimmune responses both in vitro an in vivo. The present proposal seeks funding to answer the following three questions: 1. Are enamel proteins present on the root surfaces of primate teeth? 2. What is the relationship between the occurrence and antigenicity of enamel proteins to the pathogenesis of periodontal disease? 3. What is the nature of the autoimmune response to enamel proteins in vitro? An antiserum to enamel proteins from developing primate or human teeth will be raised in rabbits according to an established protocol (Schonfeld, J. Dent. Res. 54:C72, 1975; Schonfeld, Trump, and Slavkin, Proc. Soc. Exp. Biol. Med., In Press). This antiserum will be used to look for substances which cross-react with enamel proteins on the root surfaces of primate or human teeth by radioimmunoassay, immunoelectrophoresis, and fluorescence microscopy. The participation of an enamel protein-associated autoimmune response in the pathogenesis of clinical periodontitis will be investigated by comparing lymphocyte transformations of normal and periodontal disease patient's lymphocytes in response to enamel proteins in vitro, and by checking for antibodies to enamel proteins in the sera of periodontal disease patients by immunofluorescence microscopy. The nature of the in vitro immune response will be investigated to determine whether the reaction is strictly T-cell dependent using a T-cell deficient mouse and anti-thymocyte serum. Further studies will determine if the autoimmune response to enamel proteins become more severe during the aging of NZB mice.